Amido-tartronic acid and process of making same.



-UNITED States FRITZ ACH, OF MANNHEIM, GERMANY, ASSIGNOR TO C. F. BOEHRINGER tit SOEI-INE, OF MANNHEIM-IVALDHOF, GERMANY.

AMIDO-TARTRONIC ACID AND PROCESS OF MAKING SAME.

SPECIFICATION forming part of Letters Patent No. 676,859, dated June 25, 1901. Application filed September 25, 1899. Serial No. 731.674. i pecimensfi To aZZ whom it may concern:

Be it known that I, FRITZ AOH, a citizen of the Empire of Germany, residing at Mannheim, in the Empire of Germany, have invented new and useful Improvements in Amido-' Tartronic Acids and Processes of Making the Same, of which the following is a specification. This invention relates to the manufacture of tartronic-acid derivaties; and the object of the same is the production of amido-pl1enyl tartronic acid and substitution products of the same, all of which have hitherto been unknown. I have found a method whereby one is enabled to prepare paraamidophenyltartronic acid (NI-I .O H,.G(OH) (OO H) and a series of substitution products of the same. For this purpose I employ as starting material the condensation products of alloxan with aromatic bases, which were first prepared and described by Pelizzari in Gazette Ohimzco Italicma, Vol. 17, page 412, ezfseq. Pelizzari, moreover, endeavored to obtain products of disintegration from anil-alloxan and dimethyl-anil-alloxan bythe action of alkali and 01),- served in the course of his investigations that these bodies readilygive off ammonia and carbonic acid under the influence of dilute alkalies in the cold, being thereby converted into acids which are distinguished from the start- 0 ing materials by the decreased percentage of NIL-CO. To mention an example, he ob tained from anilalloxan (O H N OQ an acid having the formula C H N O when acting on the same with a ten-per-cent. potash lye 5 (KHO) in the cold, the process being indicated in the equation:

O,UH,,N,O4+H.,O:C,II,N,O3+CO,+NII3 or c,,i-I,N,o,+KHo+H,o=o,H,N,o,K+co,+NH,+n,o. Pelizzari made the further discovery that these acids on further treatment with alkali or barium hydrate and heat will give off ammonia and carbon dioxid. He was, however, unable to obtain any tangible or definite prodnote under this treatment. I have found that well-defined products may be readily obtained if alkalies are caused to act on the addition products of alloxan and aromatic bases while heating the same. As a result of this reaction carbon dioxid and ammonia are split off, on the one hand, by reason of the complete saponification of the urea residue derived from the alloxan molecule, While, on the other hand, there are obtained alkali salts of dicarbonic acids, since the mesoxalic acid residue, which had heretofore been bound in the alloXan-nucleus, now remains bound to the benzene ring. The dicarbonic acids thus obtained have on an examination of their properties proved to be the amidophenyltartronic acids which have been hitherto unknown and which Pelizzari sought to obtain without success. If, for example, anil-alloxan (0,,H,N,0,) is submitted to the action of alkali and. heat, it is decomposed into ammonia, carbon dioXid, or a carbonate and the dialkali salt of paraamidophenyltartronic acid, the reaction taking place according to the equation: C10H,,N3O,+4KOH:NH2.C5H,,.C(OH)(COOK)2+2NH,+K2CO3 These new products of decomposition furnish for the first time a reliable proof that the products of addition of alloxan and aromatic amids obtained by Pelizzari are to be considered as amido-phenyltartronyl-ureids. They 7 correspond to the general structural formula 5 CO-NH I NH,.X.OOH 00 I coa'rn, Where NII.,.X represents a molecule, less one atom of hydrogen, of an aromatic base not substituted in the para position to the amido group. Hence the alloxan constitutes an effective means for introducing the mesoxalic or tartronic acid residue,

coon OH ooon,

which is of such great chemical activity, into the benzene molecule.

As stated above, the dialkali salts of amidophenyltartronic acid are first obtained under my process. In order to pass to the free ami- 5 do-phenyltartronic acids from these alkali salts, which are as a rule readily soluble in water, they are preferably first converted into the corresponding acid salts by acidulating concentrated aqueous solution of the same. we The acid alkali salts are thus either directly precipitated in crystalline form or they may be precipitated by the addition of alcohol. From the concentrated aqueous solutions of the acid alkali salts thus obtained the free amido-phenyltartronic acids are prepared by treating such solutions with the necessary 'and properly-computed quantities of a mineral acid. Under these conditions they are generally thrown out in the form of crystals.

1hey.are, however, redissolved and recrystal lized only with difficulty, since they are apt to be decomposed with evolution of carbon dioxid and to turn yellow when heated in aqueous or alcoholic solution. These new bodies, the amido-phenyltartronic acids,have no sharply-defined melting-point. On being heated they first turn yellowand are then decomposed as the temperature is further raised,

I the decomposition. being attended by energetic frothing. Their behavior with respect to ammoniacal silver solution is characteristic, such silver solution being reduced by them in the presence of heat, a silver mirror being formed.

Inasmuch as Pelizzari has described in detail only the three condensation products, auilalloxan,methylanilalloxan,and dim eth yl anilalloxan, I will before proceeding to my invention proper describe a further series of alloXan-addition products which have been first prepared by me and all of which I may utilize as starting products in the preparation of my new acids.

The homologues and substitution products of anil-alloxan (or para-amidophenyltartronylureid) are prepared by heating the component bodies in aqueous-alcoholic solution,generally in the presence of acetic acid. The resultant condensation products are separated while the solution is still warm. When they have been completely thrown out, they are separated from the mother-liquor, which is always colored red, by siphoning or decanting or the like, and then washed with water and a little alcohol. I have by this method obtained the following products of addition:

1. Monoethylcmilalloacan, (O lI N O Tolerably soluble in hot water or alcohol. Crystallizes in short well formed colorless prisms or spear-shaped crystals. When heated rapidly, it begins to soften at 230 centigrade, and at 243 centigrade it decomposes,

the disintegration being attended by frothing.

2. Dieihylanilallomcm, (O lI, N 0 .)-Sparingly soluble in hot water, but readily in boiling alcohol, out of which it crystallizes in the form of coarse shining prisms. It softens at 100 centigrade and melts and decomposes at from 210 to 212 centigrade.

quantities, in the form of well-shaped shining crystals.

At 205 to 200 centigradc it melts with considerable readiness to a pale-yellow liquid, from which bubbles of gas are slowly evolved.

4. Methylbenzylanil-allowcm, (O H N QJ This new body is difficultly soluble in hot water, but readily in hot alcohol, from which it crystallizes in the form of welldevel'oped prisms. It begins to soften when heated to 205 centigrade, melting at 217 to 218 centigrade, withcoincident liberation of gas and darkening in color.

5. EthylbenzylcmiZ-aZloxcm,(O lI N O Soluble with difficulty in boiling water and readily soluble in hot alcohol. From such an alcoholic solution it crystallizes in the form of flat foliated plates or prismatic crystals having a shining mother-of-pearl effect. It begins to soften at 220 centigrade and melts at 232 to 233 centigrade.

6. Phenylam'lalloxan (Diphenylamido- "mono-alloacom), (C tI N O .)1l1 the light this compound soon attains a reddish-brown color. It is but sparingly soluble in boiling water, but readily in hot alcohol. It crystallizes out of dilute alcohol in the form of fiat prisms. It begins to soften and collapse at 220 centigrade, being decomposed at 232 centigrade, this action being attended by frothing.

7. Diphenylamido d1 alloaca n, (O H N O .)-Rapidly becomes reddish brown in the light. sparingly soluble in boiling alcohol, but readily soluble in hot water, from which it crystallizes in short prisms, which are grouped together in the form of warts. It softens ates-205 centigrade, melting with decomposition at 216 centigrade.

5. Orthotoluz'dmalloascm, (O lI N O Difficultly soluble in hot alcohol and moderately in boiling water from, which. it crystallizes in the form of well-developed colorless obliquely-truncated prisms. At 220 centigrade it begins to turn a brownish color. At 240 centigrade it softens and melts with decomposition at 252 centigrade.

9. ilfono-ethyl-orthotoludinalloxan, (0 11 N O .)Sparingly soluble in hot water, from which it crystallizes in flatlaminae. Readily soluble in boiling alcohol, from which. it crystallizes in prisms aggregated in the form of crusts. Begins to soften at 200 centigrade, melting at 205 centigrade to a yellow liqquid, from which gas-bubbles are gradually evolved.

10. Ortho-(thisidrn-ctZZoman, (G H N 0 Readily soluble in hot water or alcohol. Crystallizes in colorless prisms, which soften at 220 centigrade, and melt at 240 to 242 centigrade, with strong decomposition.

11. llfonomethyl orthoanisidt'n allocctm, (O l-1 N 0 .)Readily soluble in hot water or alcohol. Crystallizes in fine needles. Begins to soften at 180 centigrade, and decomposes at 233 to 235 centigrade.

12. Orthophcnctidtn-allowcm, (C H N O Readily soluble in boiling alcohol or water. Orystallizes in coarse long colorless prisms. Begins to soften at 210 centigrade, and melt-s with decomposition at 223 to 225 centigrade.

13. .Mcta-chlorcmil-alloocan, (0 11 11 0 01)- Modcrately soluble in boiling water or alcohol. Orystallizesinsmallrectangular laminae or plates. Softens slightly at 290 centigrade, and decomposes when heated over 295 Centigrade.

14. -flIcta-chlor-dimethyZaniZ-alloxan, (0 11 N O Cl.)-Tolerably soluble in hot water. Crystallizes in coarse laminae or plates having a straw-yellow color.' On rapid crystallization it takes the form of fine needles. Softens at 230 centigrade and decomposes with frothing at 28 Centigrade.

15. IlIetct-chloro-di-ctIvyZaniLaZloxan, (0 ,11 N O,Cl.)--\Ioderately soluble in boiling water, from which it crystallizes in short welldeveloped prisms of a straw color. Readily soluble in alcohol. Softens at 220 ccntigrade and decomposes at 250 to 251 centigrade.

16. Ethylene-diphenyl diamido-d'ialloxan,

(G, lI N O. -,.)Soluble with difficulty in alco hol. From a concentrated alcoholic solution of the same it is obtained in coarse shining prisms containing one molecule O H O. At 215 centigrade these crystals stick together and they darken and are decomposed without melting at 220 centigrade. Out of boiling water or dilute alcohol it is obtained in fine acicular crystals, which soften at 190 centigrade and are decomposed at about 215 centigrade.

In order to fully disclose my invention, I will now recite a number of examples which represent what I consider the preferred method of carrying out the same".

I. Preparation of para-amiclophenyitan ironic acid (NH .G H (3 11 0.) from anilinctZZoccan.Twelve parts, by weight, of anilinalloxan are gradually introduced while stirring into twenty-six parts, by volume, of potash lye, (KHO+A,,) which has ten times the strength of normal potash lye and which has been previously heated on a boiling-water bath. The anilin-alloxan is rapidly dissolved, while at the same time an energetic evolution of ammonia takes place. As soon as all of the anilin-alloxan has goneinto solution the whole is subjected to evaporation while being stirred. Under this treatment the solution gradually thickens to a stiff crystalline semiliquid mass or paste,comprising an aggregation of fine needles, which needles consist of the di-potassiu1n salt of para'amidophenyltartronic acid. This crystalline mass is then dissolved in warm Water and the resultant so lution evaporated for driving off the ammonia as completely as possible. The residue is thoroughly dried and is then dissolved in about thirty-six parts, by weight, of water I under the influence of heat, and the resultant alkaline solution is then aoidulated with a suitable acid-such as acetic acid, for example. Under this treatment the acid potasslum salt of amidophenyltartronic acid is thrown out in the form of fine needles. This The remainder of the salt may be obtained from the mother-liquor by adding alcohol.

In order to obtain the free acid, ten parts, by weight, of the acid potassium salt are dissolved in about two hundred parts, by weight,

of warm water, 3.8 parts of potash lye (KHO +Aq) of ten times the normal strength being added. The resultant solution is treated with animal charcoal or other decolorizing agent and filtered, and the clear colorless filtrateis then treated with thirteen parts, by volume, of a solution of hydrochloric acid having six times the strength of the normal acid. Thereupon the para-amidophenyltartronic acid is thrown out in the form of shining colorless needles, such precipitation generally taking place already before the solution has cooled off. This crystalline mass after standing for a considerable time in the cold changes into a crystalline mass consisting of coarse generally square plates or tablets. After this mass has stood for some time in the cold the crystals are drained by siphoning or otherwise removing the mother-liquor and washed with some cold water. This acid is soluble in hot water with tolerable case, more difficultly in alcohol. It cannot, however, be recrystallized from these solutions, since 011 heating the same carbonic acid is very soon evolved, the solutions becoming intensely yellow. Its formula is Nfl Odl C/ ll O or coo1 Mr,.c,i-i,.con cooH.

The normal alkali salts, (including ammonium salt,) which are readily soluble in water, may be converted into the acid salts, which are only difficultly soluble in cold water, by reacting thereon with acetic acid.

Amidophenyl-tartronic acid is readily soluble without decomposition in dilute mineral acids and also in concentrated hydrochloric and sulfuric acids. On heating these solutions carbon dioxid is very soon liberated. This acid has no sharply-defined meltingpoint. On heating the same it begins to turn yellow at 150 centigrade, and from that point it becomes progressively darker with the elevation of temperature until decomposi= tion takes place at from 215 to 220 centigrade, the decomposition being accompanied by frothing. An ammoniacal solution of the acid reduces a silver solution in the heat with formation of a shining silver mirror.

II. Preparation of pam-amido-meta-toluyltctrtron'ic acid from ortho-ioluidinallowcmn-Twehtyhve parts, by weight, of orthotoluidin -alloxan are gradually introduced into fifty-two parts, by volume, of ten times normal potash lye, (KHO+A(1,) which has been previously heated on a boiling-water bath, the introduction being accompanied by stirring. After the solution has been effected the same is evaporated to completely drive off the ammonia. The residual crystalline mass is then dissolved in water, and this solution is also evaporated. The residue, which should be as dry as possible, is brought into solution with a small amount of water (three parts, by volume) and application of heat, (40 centigrade.) The clear brownish yellow solution thus obtained is then slightly acidulated with any suitable acidsuch, for example, as acetic acid. Upon adding to this solution from three -to four parts, by volume, of alcohol the acid potassium salt of paraamido-meta-toluyltartronic acid is thrown out, and after the same has stood for some time (eight toten hours)2in the cold the motherliquor is drained from the precipitate in any suitable mannersuch, for example, as siphoning or decanting.

To obtain the free acid,the mono-potassium salt is dissolved in two parts, by weight, of water at a gentle heat, and hydrochloric acid is then added until the same colors Congo paper. From the solution thus prepared the new compound, paraamido metatolnyltartronic acid, begins to precipitate while still warm in the form of needles grouped in star shaped aggregations, which are only slightly colored. The crystallization is completed after the solution hasstood for some time in the cold. This new acid, whose formula is NH .G H .O,H O or (NH2) on )o er o 9 3 oooH,

is readilysoluble in mineral acids and dilute alkalies, including ammonia. An ammoniacal solution of the same will reduce an ammoniacal silver solution when heated, a silver mirror being formed. It begins to turn yellow when heated to over 150 centigrade. On raising the temperature above this point the compound gradually and progressively becomes darker until it is dark brown. At 194 to 195 centigrade it is decomposed, the decom position being accompanied by foaming or frothing.

III. Preparation ofpara-eihg Zene-di-ami dophenyltarironic acid from ethylene dipheng Z diamido diallooccm. Five parts, by weight, of ethylene-dipl1enyldiamido-dialloxan are dissolved Warm in 10.5 parts, by volume, (corresponding to ten and one-half molecules,) of a solution of hydrate of potassium having ten times the strength of normal potash lye. The solution is evaporated until crystallization takes place. The crystals are then dissolved in water, and the solution is again evaporated. The crystalline residue is then taken up with a minimum quantity of warm water (40 centigrade) and then acidulated with a suitable acid-such as, preferably, glacial acetic acid-and finally treated with alcohol. As a result of this treatment a concentrated aqueous solution of the acid potassium salt is first separated, which solution subsequently, after standing for some time,

will be found to be in the form of a thick syrup covered by a layer of alcoholic lye. This supernatant lye may be poured off from the said syrup. The acid potassium salt of the new compound thus freed from the lye is then triturated with alcohol, whereby it is caused to assume a crystalline. structure. The crystallized mono-potassium salt thus obtained is then dissolved warm in a little water, (about three parts, by weight.) The resultant red solution is then treated with a decolorizing agent, such as animal charcoal, and filtered, and the filtrate is slightlyacidulated with a suitable acid-such as hydrochloric acid, for example. The new compound, paraethylene-diamido-diphenyltartronic acid, is thus obtainedin the form of a slightly-colored fine crystalline precipitate,Which will formin spheroidal aggregates when crystallization takes place slowly. This new acid is readily soluble in alkalies and mineral acids. An ammoniacal solution of the same reduces an ammoniacal silver solution in the presence of heat, with formation of a silver mirror. On heating the said new acid above 300 centigrade it gradually becomes dark brown, and it is decomposed without melting at a temperature above 400 centigrade. The formula of the new acid is C H,.N H (O H .O H O or OOH In addition to the above the following compounds belonging to this class have been prepared by me by proceding according to the method above described and substituting the corresponding condensation products, as indicated below.

IV. Paramezfhyl-amidopheng Ztarironic acid from mcthylanii aZZoxan.-This new acid, whose formula is 0H,.HN. O IL. 0 11 0 crys. tallizes in fine concentric or radially-grouped needles, which when allowed to remain in the mother-liquor or solution change to coarse flat prisms. When heated beyond 120 centigrade and about 180 centigrade, the mass, which has become orange-colored, decomposes, this change being accompanied by frothing.

V. Preparation of paradimethyl-amidephenyliartronic acid from dimeihg lanilallowan. (Formula: (CHQ ND H .C H O Orystallizes in coarse flat prisms pointed in one direction. Decomposes at 109 to 110 centigrade, the decomposition being preceded by slight coloration and attended by frothing or eifervescence.

VI. Para-ethylamido-phcnyltartronic acid from mono-ethylaniZ-alloman.This new acid softens at 125 centigrade and decomposes at about 163 centigrade. Its formula is O l-l NH. O IL. C H O VII. Paradiethylamido pheng Ztartronic acid from diethyZaniZ-alloxan.-Orystallizes in fine needles which are decomposed with attendant frothing at 107 to 108 centigrade. Formula: (O H N.C H,.O I-I O VIII. Paramido metamcthoxyphcnyltarironic acid from OTtItO-Cldtttdtlt-CLZZOILCLH. Gryst-allizes in short coarse prisms,which turn yellow at150 centigrade and which are decomposed at 187 to 188 centigrade, the decomposition being accompanied with darkening and frothing. Formula:

IX. Paramcthylamido meta mcthomyphem ltartron'ic acid from mcthg lorthoa-msidtna7loitan.-Orystallizes in fine needles, which become yellow at 120 centigrade and which are decomposed gradually at 135 centigrade, with attendant frothing or eifervescence. Formula: OH .NH(OH O')C H .C H O X. Paramt'd 0 meta-cthoxyphenyltartronic acidfrom orzho-phenetidin-allowan.Grystallizes in fiatcoarse needles, turns yellow at 140 centigrade, and decomposes at about 175 centigrade, with attendant frothing and darkening of color. Formula:

XI. Paramidaorthochlorophenyltartronic acid from mcta-chloram'l-aZZoacan.-Crystallizes in fine needles, which turn yellow at about 145 centigrade and which melt with decomposition at 198 to 199 ccnligrade. Formula: NI-I .O I-I .Ol.O l'l O XII. Parabcnzylamt'do phenyltartronic acid from bcnzylaml-allowcm.Is precipitated in the form of an indistinctly-crystallized straw-colored powdergwhich melts at about 137 centigradeavith attendant frothing. For mula: C H NH. C 11 G l-T 0 ,XIII. Paraphcm Zamido phenyltartronic acid from diphem ZamtdaaZZoman.-Orystallizesin shining mother-of-pearl-colored scales or in time needles, which melt at from 125 to 127 centigrade with decomposition. Formula: C H NH.G H .C H O XIV. Paracthylamtdomtetatoluylta rfroitic acid from ethyl-orthotolatdtn-alloman.Formnla: O H .NH. O H 0 11 0 Thelfollowin g acids of this series have not hitherto been isolated in crystalline form, but have been obtained in the form of their acid potassium salts:

XV. Para cthylbenzg Zamido phem Ztartrom'c acid from ethyZbcnzg Zaml-alloaaot.- Formula: O H .C II,.N.0 H .(3 11 0 XVI. Paradtmcthg lamtdo ortho chlorojfltGHJUZ-tCH'tTORtC acid from metachlorodimcthylamlalloacan. Formula (cH,),N.o,H,.oi.o,I-i,o,. QYVII. Parad'icthylamtdo-orthochlorop7ic- X V III. Para-imtdodiphang Z-tartron fc aci d from dzphcng lcmmdo-dt-alloazan. Form ula As Will be seen from the above, my invention, broadly considered, consists in splitting off the urea residue from a condensation product ot alloXan with an aromatic base, which may be done by submitting the same to the action of an alkali and heat, and, further, in the subsequent solution of the resultant normal alkali salt of the new acids in water, followed by evaporation and acidulation to form the acid alkali salt, and, finally, in dissolving the latter product and treating with a mineral acid, such as hydrochloric or equivalent acid, to form the free acid.

It should be noted that instead of the acetic acid set forth above in the preparation of the acid alkali salts of my new acids other equiv alent acids may be employed and also that the hydrochloric acid set forth in the final step of the preparation of my new acids may be replaced by other mineral acids.

From the above description and considera-' tions it follows, moreover, that the new acids, (the amido-phenyltartronic acids) correspond to the general structural formula:

M te cooH, where Y representsa molecule of an aromatic base less one atom of hydrogen. For paramidophen yltartronic acid prepared from anilin-alloxanc. Y corresponds to the group NH U H, or

the formula of this amido-phenyltartronic acid being H H COOH H H COOH.

These acids, it will be noted from the for-' mula, are all bibasic acids. A large number of them have the property of turning yellow at a raised temperature, and on further raising the temperature they turn darker in most cases. All of them, so far as investigated, decompose at higher temperatures, and therefore have no melting-point. This decomposition is generally attended by frothing or effervescence, due to the evolution of gas. The reaction whereby they are generated from the addition products of alloXan and an aromatic base is indicated by the equation for amidophenyl-tartronic acid.

H H COOK H.,N -doH +2NH,+K,00,

H H COOK and, generally, for the preparation of all the amido phenyl-tartronic acids by the equation:

or structurally:

What I claim, and desire to secure by Letters Patent of the United States, is-

1. The process which consists in heatinga condensation product of-alloxan and an aromatic base with an alkali.

2. The process which consists in dissolving a normal alkali salt of an amido-phenyltartronic acid in water and acid ulating the solution, whereby the acid alkali salt of such acid is thrown out.-

3. The process which consists in dissolving a normal alkali salt of amido-phenyltartronic acid in water acidulating the solution and adding alcohol thereto for throwing out the corresponding acid alkali salt.

4. The process which consists in dissolving an acid alkali salt of an amido-phenyltartronic acid and acidulating the solution with a mineral acid.

5. The process which consists in dissolving an acid alkali salt of an amido-phenyltaie tronic acid in water and acidulating the solution with hydrochloric acid.

6. The process which consists in dissolving an acid alkali salt of an ainido-phenyltartronic acid and adding thereto a decolorizing agent, then filtering and finally adding a mineral acid to the filtrate whereby the free amido-phenyltartronic acid is precipitated.

7. The process which consists in treatinga condensation product of alloxan and an aromatic base with an alkali, then dissolving the resultant normal alkali salt of amido-phenyltartronic acid in water and acidulating the solution and'finally dissolving the resultant acid alkali salt and treating the solution with a mineral acid'to throw out the free amidophenyltartronic acid.

8. The process which consists in heating a condensation productot'an'alloxan and an aromat-ic base with an alkali, then dissolving the resultant product in water and acidulating the solution and adding alcohol and then dis- 5o as hereinbefore set forth, the same being a bibasic acid which has no defined meltingpoint but decomposes when heated to temperatures where it leaves the solid state, and

which reduces silver solutions with the formation of a silver mirror.

10. Asanew chemical compound, an amidotartronic acid of the aromatic series having the formula above given, the same being a bibasic acid which turns yellow at a raised temperature and assumes adark color on still further raising the temperature, which has no defined melting-point but decomposes with efifervescence when heated to temperatu res at which it leaves the solid state and which reduces silver solutions with the formation of a silver mirror.

In testimony whereof I have signed my 8:

name to this specification in the presence of two subscribing Witnesses.

FRITZ AOH. Witnesses:

MAX BURBNER, JAcoB ADRIAN. 

